A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of ABT-888 in Combination With Whole Brain Radiation Therapy in Subjects With Brain Metastases

Further study details as provided by AbbVie:

Primary Outcome Measures:

Determine the maximum tolerated dose of ABT-888 in combination with whole brain radiation therapy [ Time Frame: ABT-888 will be dose escalated until the largest dose is reached that is felt to be safe based on safety information from all subjects. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Safety Assessment Physical and Neurological Exam [ Time Frame: be performed at all study visits, final and follow-up visit ] [ Designated as safety issue: Yes ]

Safety Assessment Mini-Mental State Examination [ Time Frame: be performed at all study visits, final and follow-up visit ] [ Designated as safety issue: Yes ]

Safety Assessment Laboratory testing [ Time Frame: be performed at all study visits, final and follow-up visit ] [ Designated as safety issue: Yes ]

This is an open label study; therefore, there are no numbered/labeled study arms.

This is a dose escalation study, ABT-888 dose will be escalated in conjunction with two schedules of whole brain radiation therapy (WBRT). Subjects may be treated WBRT for 3 weeks (15 days) or 2 weeks (10 days).

Drug: ABT-888

Oral Capsules

Other Name: veliparib

Radiation: Whole Brain Radiation Therapy

15 fractions of 2.5 Gy over 3 weeks to a total dose of 37.5 GY or 10 fractions of 3.0 Gy over 2 weeks to a total dose of 30 Gy

Other Name: WBRT

Detailed Description:

This is a Phase 1, multicenter, dose-escalation study evaluating the safety, tolerability and pharmacokinetics of the PARP inhibitor ABT-888 in combination with conventional whole brain radiation therapy (WBRT) in the treatment of subjects with solid tumors metastatic to the brain.

Pathologically or radiographically confirmed metastatic disease in the brain. Subjects with non-measurable lesions, including leptomeningeal carcinomatosis, are eligible.

WBRT is clinically indicated, with the exception of prophylactic treatment.

Karnofsky Performance Status (KPS) greater than or equal to a score of 70.

Adequate hematology, renal and hepatic function.

Both men and women of childbearing potential must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and up to 2 months following completion of protocol therapy.

Total abstinence from sexual intercourse (minimum one complete menstrual cycle)

Subject is capable of understanding and complying with parameters as outlined in the protocol.

Subject or the subject's legally acceptable representative has voluntarily signed and dated the informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

Brain metastases secondary to germ cell tumor or lymphoma malignancy.

Primary central nervous system (CNS) neoplasm.

Prior or concurrent administration of the following therapies or treatments:

Prior treatment with WBRT

SRS performed less than 14 days prior to WBRT D1, or is scheduled to occur within 30 days of the last WBRT session

Last dose of chemotherapy, immunotherapy, biologic therapy, or investigational therapy was less than 14 days prior to WBRT D1. Bisphosphonates, hormone modification therapy, and trastuzumab are permitted without restriction

History of immediate or delayed hypersensitivity reaction or other contraindication to contrast agents including but not limited to gadolinium and iodine

Previous enrollment in this study or another study involving the investigation of ABT-888, with the exception of receiving a single dose of study drug.

Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-888 and/or WBRT.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00649207